[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

OBJECTIVES: To investigate the active ingredients in Hedyotis diffusa-Scutellaria barbata D. Don and the main biological processes and signaling pathways mediating their inhibitory effect on primary hepatocellular carcinoma (HCC). METHODS: The core intersecting genes of HCC and the two drugs were screened from TCMSP, Uniport, Genecards, and String databases using Cytoscape software, and GO and KEGG enrichment analyses of the intersecting genes were conducted. Molecular docking between the active ingredients of the drugs and the core genes was carried out using Pubcham, RCSB and Autoduckto to identify the active ingredients with the highest binding energy, whose inhibitory effect on HepG2 cells was verifies using CCK-8 assay, flow cytometry and Western blotting. RESULTS: TP53 and ESR1 were identified as the core genes of HCC and the two drugs. GO and KEGG analyses showed that the two genes were mainly involved in regulation of apoptotic signaling pathway, cell population proliferation, methane raft, and protein kinase activity, and participated in the signaling pathways of apoptosis, proteoglycans in cancer, PI3K Akt signaling pathway, and hepatitis B. Molecular docking studies showed that the active ingredients of the drugs could be docked with TP53 and ESR1 genes under natural conditions, and ursolic acid had the highest binding energy to ESR1 (-4.98 kcal/mol). The results of CCK-8 assay, flow cytometry and Western blotting all demonstrated significant inhibitory effect of ursolic acid on HepG2 cells. CONCLUSIONS The inhibitory effect of Hedyotis diffusa-scutellariae barbatae on HCC is mediated by multiple active ingredients in the two drugs.
Humans ; Molecular Docking Simulation ; Liver Neoplasms/drug therapy* ; Hep G2 Cells ; Network Pharmacology ; Carcinoma, Hepatocellular/drug therapy* ; Hedyotis/chemistry* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Apoptosis/drug effects* ; Estrogen Receptor alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

OBJECTIVE To investigate the inhibitory effect and the possible mechanism of hydrogen sulfide （H2S） on the proliferation of cardiac fibroblasts. METHODS The heart of neonatal SD rats was collected， and cardiac fibroblasts were separated with differential centrifugation. Using sodium hydrosulfide as the donor of H2S， the effects of H2S on the proliferation of cardiac fibroblasts induced by angiotensin Ⅱ （Ang Ⅱ）， hydroxyproline content and the expression of sirtuin 3 （SIRT3） protein were detected. After SIRT3 knockdown with siRNA technology， the effects of H2S on the proliferation of cardiac fibroblasts induced by Ang Ⅱ， hydroxyproline content， the expressions of collagen Ⅰ （Col Ⅰ）， collagen Ⅲ （Col Ⅲ ） and optic atrophy protein 1 （OPA1） were detected. RESULTS H2S could inhibit the proliferation of Ang Ⅱ-induced cardiac fibroblasts， reduce the content of hydroxyproline and increase the expression of SIRT3 （P＜0.05）. After down-regulating the expression of SIRT3 with siRNA technology， the inhibition of H2S on the proliferation of Ang Ⅱ-induced cardiac fibroblasts and the reduction of hydroxyproline content were both inhibited， and the effect of H2S on reducing the expression of Col Ⅰ and Col Ⅲ and enhancing the expression of OPA1 was also significantly weakened. CONCLUSIONS H2S inhibits the proliferation of Ang Ⅱ -induced cardiac fibroblasts through increasing the expression of SIRT3.

Background::The complete mesogastrium excision (CME) based on D2 radical gastrectomy is believed to significantly reduce the local-regional recurrence compared with D2 radical gastrectomy in advanced gastric cancer, and it is widely used in China. This study aimed to explore whether D2 + CME is superior to D2 on surgical outcomes during gastrectomy from Chinese data.Methods::Feasible studies comparing the D2 + CME (D2 + CME group) and D2 (D2 group) published up to March 2020 are searched from electronic databases. The data showing surgical and complication outcomes are extracted to be pooled and analyzed.Results::Fourteen records including 1352 patients were included. The D2 + CME group had a shorter mean operative time (weighted mean difference [WMD] = -16.72 min, 95% confidence interval [CI]: -26.56 to - 6.87 min, P < 0.001), lower mean blood loss (WMD = -39.08 mL, 95% CI: -49.94 to -28.21 mL, P < 0.001), higher mean number of retrieved lymph nodes (WMD = 2.13, 95% CI: 0.58-3.67, P = 0.007), shorter time to first flatus (WMD =-0.31 d, 95% CI: -0.53 to - 0.10 d, P = 0.005), and postoperative hospital days (WMD =-1.09, 95% CI: -1.92 to -0.25, P = 0.010) than the D2 group. Subgroup analysis suggested that the advantages from the D2 + CME group were obvious in traditional open radical gastrectomy, proximal gastrectomy, and distal gastrectomy compared with D2 group. The evaluations of post-operative complications showed that the patients who underwent D2 + CME had a lower incidence of post-operative complications than the patients who underwent D2 surgery alone (relative risk [RR] = 0.65, 95% CI: 0.45-0.87, P = 0.003). The D2 radical gastrectomy plus CME improved 3-year overall survival (OS) (RR = 1.16, 95% CI: 1.02-1.32, P = 0.020) and lowered the local recurrence rate (RR = 0.51, 95% CI: 0.28-0.94, P = 0.030). The patients undergoing laparoscopic surgery or total gastrectomy had more significant advantages compared between D2 + CME and D2 groups in 3-year OS. Conclusion::The data from China show that D2 radical gastrectomy plus CME are reliable procedures and safety compared to D2 radical gastrectomy with faster recovery, lower risk, and better prognosis.

Objective:To investigate the application value of esophagogastric anastomosis with double muscle flap plasty in total laparoscopic radical resection of proximal gastric cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients undergoing radical resection of proximal gastric cancer in Cancer Hospital of China Medical University from January to December 2020 were collected. All 5 cases were male, aged from 57 to 72 years, with a median age of 65 years. All 5 patients underwent total laparoscopic radical resection of proximal gastric cancer combined with esophagogastric anastomosis with double muscle flap plasty. Observation indicators: (1) operative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect postoperative anastomosis, esophageal reflux, nutritional status, quality of life, tumor recurrence and metastasis of patients up to February 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Operative situations: all 5 patients underwent surgery successfully. The operation time, time of esophagogastric anastomosis with double muscle flap plasty, number of lymph node dissected, volume of intraoperative blood loss, length of surgical incision of 5 patients were (316±41)minutes,(109±11)minutes, 26±4, (48±12)mL, (3.4±0.4)cm, respectively. Results of intraoperative rapid frozen section pathological examination showed negative of esophageal margin. (2) Postoperative situations: the time to postoperative initial flatus, time to postoperative initial food intake, during of postoperative hospital stay, cost of treat-ment of 5 patients were (4.8±1.5)days, (5.8±1.5)days, (11.6±2.1)days and (5.5±0.4)×10 4 yuan, respectively. Results of postoperative pathological examination of 5 patients showed gastric adeno-carcinoma in all 5 patients including 4 cases with moderately and poorly differentiated adeno-carcinoma and 1 case with highly differentiated adenocarcinoma, with the TNM staging of pT1a-3N0-1 M0 stage. Of the 5 patients, 1 case underwent postoperative mild pneumonia and was cured by conservative treatment such as anti-infection and promotion of sputum evacuation. (3) Follow-up: all 5 patients were followed up for 2 to 12 months, with a median follow-up time of 6 months. Of the 5 patients, 4 cases underwent anastomotic patency and 1 case underwent mild anastomotic stenosis who was improved after endoscopic treatment. None of the 5 patients underwent reflux esophagitis. The body mass index, the score of nutritional risk screening 2002, the score of patient-generated subjective global assessment and the score of tumor patient quality of life of 5 patients were 21 kg/m 2(range, 19-27 kg/m 2), 2(range, 1-2), 2(range, 1-3) and 47(range, 42-52), respectively. None of the 5 patients underwent tumor recurrence or metastasis. Conclusion:Esophagogastric anas-tomosis with double muscle flap plasty can be used in total laparoscopic radical resection of proximal gastric cancer which will lead to satisfactory short-term efficacy.

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

Objective To investigate the regulation effects of Ngn2 gene transfection on retinal neuron differnetion in three-dimentional optic vesicle (OV) of mice.Methods OV was cultured in vitro using mouse induced pluripotent stem cells (iPSC) under specific conditions.During OV culture,it was transfected multiple times by lentivirus-mediated Ngn2 gene and then it was induced after maturation.The cells were specificly differentiated toward retinal nerve cells in OV.Using the green fluorescent protein (EGFP) gene as control,the differentiation of retinal nerve cells in OV was detected by immunohistochemistry.Reverse transcription PCR and Western blot were used to quantitatively detect the expressions of retinal neuron-specific proteins Pax6,Islet1 and Brn3b.Results The mouse iPS-derived OV was successfully cultured.The number of neural cells in the OV transfected with the Ngn2 gene was increased by the lentiviral-mediated lentivirus.The expressions of PAX6,Islet1 and Brn3b in the Ngn2 transfection group were significantly higher at the gene and protein levels than those in the control group,with significant differences between the two groups (P＜0.05).Conclusions The Ngn2 gene can effectively increase the number of retinal neuron differentiation in OV and make in vitro cultured OV more mature and form a more perfect retinal cell neural circuit.

Objective To observe the clinical effects of arthroscopic reconstruction for anterior cruciate ligament ( ACL ) tear using tension-relieving technique and enhanced recovery after surgery ( ERAS ) . Methods Between May 2014 and June 2016, 80 patients with ACL tear were randomly di-vided into 2 equal groups. The experimental group was treated with arthroscopic reconstruction using hamstring tendon autograft and tension-relieving technique followed by ERAS; the control group was treated with arthroscopic reconstruction using hamstring tendon autograft only followed by conventional postoperative re-covery. The 2 groups were compared in terms of knee flexion angles at postoperative 2nd, 4th and 8th weeks, and the IKDC ( International Knee Documentation Committee ) , HSS ( Hospital for Special Surgery ) , and Lysholm scores at postoperative 3rd, 6th and 12th months. Results The 80 patients obtained an average follow-up of 12. 3 ± 1. 7 months. Arthroscopy one year postoperation revealed fine ACL growth without laxity or other complications in the experimental group. Joint stiffness appeared in one case at 2 months postoperation and ACL laxity was observed in 3 cases by arthroscopy at 12 months postoperation in the control group. The knee flexion angles at postoperative 2nd, 4th and 8th weeks, and the IKDC, HSS and Lysholm scores at postoperative 3rd, 6th and 12th months in the experimental group were significantly better than those in the control group ( P <0. 05 ) . In both groups, the IKDC, HSS and Lysholm scores at postoperative 3rd, 6th and 12th months and the knee flexion angles at postoperative 2nd, 4th and 8th weeks were all significantly im-proved than the preoperative values ( P <0. 05 ) . Conclusion In arthroscopic reconstruction for ACL tear, tension-relieving technique combined with ERAS can promote functional recovery of the knee and reduce postoperative complications, facilitating early recovery of sports function.

Objective: To investigate the clinical value of endoscopic ultrasonography (EUS) and Multi-slice Spiral CT (MSCT) in the preoperativestaging of tumor(T) and lymph node (N) metastasis in patients with SiewertⅡand Ⅲ typeadenocarcinoma of esophagogastric junction(AEG). Methods: Clinical data of 145 Siewert Ⅱ and Ⅲ type AEG patientswithout preoperative chemoradiotherapy were retrospectively reviewed. Theyall received preoperative EUS and MSCT examination and underwent surgical resection, and the results of EUS and MSCT were compared with their postoperative pathologic staging. Results: The sensitivity, specificity, and accuracy of EUS for T stage in Siewert Ⅱ and Ⅲ type AEG were higher than those of MSCT. The total accuracy of EUS and MSCT were 90.3% and 63.5%, respectively, and the difference was statistically significant (χ²=29.52, P<0.01). The sensitivity of EUS for T1, T2 and T3 were 89.5%, 91.1% and 85.2%, respectively, which were significantly higher than 42.1%, 66.7% and 29.6% of MSCT (χ²=9.47, P<0.01 for T1; χ²=8.07, P<0.01 for T2; χ²=17.40, P<0.01 for T3). In addition, the total accuracy of EUS and MSCT for lymph node metastasis status of Siewert Ⅱ and Ⅲ type AEG were 75.9% and 64.8%, respectively, showing a statistically significant difference(χ²=4.23, P=0.04). The sensitivity of EUS for N1 and N2 were 82.1% and 79.2%, respectively, which were significantly higher than 53.6% and 60.4% of MSCT (χ²=5.24, P=0.02; χ²=4.48, P=0.03). There was no statistical significance for sensitivity of EUS and MSCT in N0 and N3 (P>0.05). Conclusion EUS diagnosis of T and N staging in Siewert Ⅱ/Ⅲ type AEG showed significantly greater performance than MSCT.